Given that AMT-130 is delivered via an intrastriatal AAV vector, what have we learned about optimal dosing, vector distribution, and potential immunogenicity risks that could influence broader clinical use or future gene therapy approaches in Huntington’s disease?

Which patient subpopulations (e.g. by CAG repeat length, disease stage at infusion, baseline cUHDRS) appear to derive the most benefit, and are there any biomarker correlates (e.g. MRI, CSF huntingtin levels) predictive of response or safety?

How do the observed effects of AMT-130 compare with existing or emerging therapies in Huntington’s disease, and where do you envision this gene therapy fitting into standard of care (e.g. combination with symptomatic treatments, timing of intervention)?

are there rumblings amongst the community/experts on what sort of internal decision-making occurred to prompt the FDA's flip flop? 

What were initial impressions when evaluating early results against the sham-surgery arm? If the relative parity in results was attributed to variance (i.e. small sample size, not enough time for symptom progression, etc) - does the three year timeframe from September data still pose similar risks? 

The skepticism on some of the questionnaire based results is fair. What does he think of the NfL measures which the team referenced as a secondary endpoint? 

What would confirmatory trial look like just a larger "n" and the same design?